Santhosh A Upadhyaya1, Giles W Robinson1, Arzu Onar-Thomas2, Brent A Orr3, Catherine A Billups1,2, Daniel C Bowers4, Anne E Bendel5, Tim Hassall6, John R Crawford7, Sonia Partap8, Paul G Fisher8, Ruth G Tatevossian3, Tiffany Seah9, Ibrahim A Qaddoumi1,10, Anna Vinitsky1, Gregory T Armstrong1,11, Noah D Sabin12, Christopher L Tinkle13, Paul Klimo14,15,16, Danny J Indelicato17, Frederick A Boop14,15,16, Thomas E Merchant13, David W Ellison3, Amar Gajjar1,18. 1. Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 2. Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 3. Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 4. Departments of Pediatrics and Neurological Surgery, University of Texas Southwestern Medical School/Children's Health, Dallas, Texas, USA. 5. Department of Hematology Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA. 6. Department of Medicine, Queensland Children's Hospital, South Brisbane, Australia. 7. Department of Neurosciences and Pediatrics, University of California San Diego and Rady Childrens Hospital, San Diego, California, USA. 8. Department of Neurology & Division of Child Neurology, Stanford University, Palo Alto, California, USA. 9. Department of Medicine, University of Cambridge, London, UK. 10. Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 11. Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 12. Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 13. Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 14. Department of Surgery, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 15. Semmes-Murphey Clinic, Memphis, Tennessee, USA. 16. Department of Neurosurgery, University of Tennessee and Le Bonheur Children's Hospital, Memphis, Tennessee, USA. 17. Department of Radiation Oncology, University of Florida, Jacksonville, Florida, USA. 18. Department of Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Abstract
BACKGROUND: This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. METHODS: Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier. RESULTS: One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89). CONCLUSIONS: In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.
BACKGROUND: This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. METHODS: Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier. RESULTS: One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89). CONCLUSIONS: In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELAtumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.
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